Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder.

Objective: To analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes. Methods: 193 children with ADHD were included in our study from February 2017 to February 2020 in the Children's ADHD Clinic of the author's medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the "corplot" package was used for correlation analysis. Results: Among the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD. Conclusion: There were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

The long-range white matter microstructural alterations in drug-naive children with ADHD: A tract-based spatial statistics study.

BACKGROUND: To investigate WM alterations, particularly the changes in long-range fibers, in drug-naive children with attention deficit hyperactivity disorder (ADHD), we conducted tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) data. MATERIALS AND METHODS: In this study, 57 children with ADHD and 41 healthy controls (HCs) were enrolled. None of the enrolled ADHD children received any medication before data collection. WM changes were then correlated with clinical symptoms, including the hyperactivity index score and the impulsivity score. RESULTS: ADHD children demonstrated decreased FA in the right forceps major, left inferior fronto-occipital fasciculus, and left genu Internal capsule. Moreover, higher RD was observed in the right forceps major, superior longitudinal fasciculus, and forceps major. The results of linear regression analysis including learning problem score, hyperactivity index score and impulsivity score showed that higher earning problem and hyperactivity/impulsivity symptom scores were negatively correlated with the mean FA value in the right forceps major, left IFOF and left genu Internal capsule. CONCLUSION: Our results demonstrate that microstructural WM alterations and changes in the long-range WM connections are present in children with ADHD. We speculate that these changes may relate to the symptoms of hyperactivity and impulsivity.

Sex differences in microstructural alterations in the corpus callosum tracts in drug-naïve children with ADHD.

Widespread alterations in the corpus callosum (CC) microstructure and organization have been found in children with attention-deficit/hyperactivity disorder (ADHD); however, few studies have investigated the diffusion characteristics and volume of transcallosal fiber tracts defined by specific cortical projections in ADHD, which is important for identifying distinct functional interhemispheric connection abnormalities. In the current study, an automated fiber-tract quantification (AFQ) approach based on diffusion tensor imaging identified seven CC tracts according to their cortical projections and estimated diffusion parameters and volume among 76 drug-naïve ADHD patients (53 boys and 23 girls) and 37 typically developing children (TDC) (20 boys and 17 girls) matched for age, IQ, and handedness. We found significantly lower fractional anisotropy (FA) in the occipital and superior parietal tracts and higher mean diffusivity (MD) in the posterior, superior parietal and anterior frontal tracts in children with ADHD compared with TDC. In addition, lower FA and higher radial diffusivity (RD) in the occipital callosal tract were significantly associated with higher hyperactivity and impulsivity performance in ADHD. In addition, sex-by-diagnosis interactions were observed in the occipital, posterior and superior parietal tracts. Girls with ADHD showed decreased FA and volume in the occipital tract, which were significantly associated with increased impulsivity performance and poor response control, and increased MD in the posterior and superior parietal callosal tracts, which were significantly associated with increased inattention performance, whereas boys with ADHD merely showed decreased volume in the frontal tract. Our results elucidated that sex-specific alterations in the CC tracts potentially underlie ADHD symptomatology and further suggested a differential contribution of abnormalities in different CC tracts to impulsivity and inattention among girls with ADHD.

Different effects of the DRD4 genotype on intrinsic brain network connectivity strength in drug-naïve children with ADHD and healthy controls.

The dopamine D4 receptor gene (DRD4) has been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). Recent studies have linked DRD4 to functional connectivity among specific brain regions. The current study aimed to compare the effects of the DRD4 genotype on functional integrity in drug-naïve ADHD children and healthy children. Resting-state functional MRI images were acquired from 49 children with ADHD and 37 healthy controls (HCs). We investigated the effects of the 2-repeat allele of DRD4 on brain network connectivity in both groups using a parameter called the degree of centrality (DC), which indexes local functional relationships across the entire brain connectome. A voxel-wise two-way ANCOVA was performed to examine the diagnosis-by-genotype interactions on DC maps. Significant diagnosis-by-genotype interactions with DC were found in the temporal lobe, including the left inferior temporal gyrus (ITG) and bilateral middle temporal gyrus (MTG) (GRF corrected at voxel level p < 0.001 and cluster level p < 0.05, two-tailed). With the further subdivision of the DC network according to anatomical distance, additional brain regions with significant interactions were found in the long-range DC network, including the left superior parietal gyrus (SPG) and right middle frontal gyrus (MFG). The post-hoc pairwise analysis found that altered network centrality related to DRD4 differed according to diagnostic status (p < 0.05). This genetic imaging study suggests that the DRD4 genotype regulates the functional integration of brain networks in children with ADHD and HCs differently. This may have important implications for our understanding of the role of DRD4 in altering functional connectivity in ADHD subjects.

Altered Variability and Concordance of Dynamic Resting-State fMRI Indices in Patients With Attention Deficit Hyperactivity Disorder.

Objective: Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in children, which is characterized by inattention, hyperactivity and impulsivity. Using resting-state functional magnetic resonance imaging (R-fMRI), the alterations of static and dynamic characteristics of intrinsic brain activity have been identified in patients with ADHD. Yet, it remains unclear whether the concordance among indices of dynamic R-fMRI is altered in ADHD. Methods: R-fMRI scans obtained from 50 patients with ADHD and 28 healthy controls (HC) were used for the current study. We calculated the regional dynamic changes in brain activity indices using the sliding-window method and compared the differences in variability of these indices between ADHD patients and HCs. Further, the concordance among these dynamic indices was calculated and compared. Finally, the relationship between variability/concordance of these indices and ADHD-relevant clinical test scores was investigated. Results: Patients with ADHD showed decreased variability of dynamic amplitude of low-frequency fluctuation (dALFF) in the left middle frontal gyrus and increased one in right middle occipital gyrus, as compared with the HCs. Besides, ADHD patients showed decreased voxel-wise concordance in the left middle frontal gyrus. Further, lower voxel-wise concordance in ADHD's left middle frontal gyrus was associated with more non-perseverative errors in Wisconsin Card Sorting Test, which reflects worse cognitive control. Conclusion: Our findings suggest that variability and concordance in dynamic brain activity may serve as biomarkers for the diagnosis of ADHD. Further, the decreased voxel-wise concordance is associated with deficit in cognitive control in ADHD patients.

Larger thalamus correlated with inattentive severity in the inattentive subtype of ADHD without comorbidity.

Previous studies of brain structural abnormalities in attention-deficit/hyperactivity disorder (ADHD) samples scarcely excluded comorbidity or analyzed them in subtypes. This study aimed to identify neuroanatomical alterations related to diagnosis and subtype of ADHD participants without comorbidity. In our cross-sectional analysis, we used T1-weighted structural MRI images of individuals from the ADHD-200 database. After strict exclusion, 121 age-matched children with uncomorbid ADHD (54 with ADHD-inattentive [iADHD] and 67 with ADHD-combined [cADHD]) and 265 typically developing control subjects (TDC) were included in current investigation. The established method of voxel-based morphometry (VBM8) was used to assess global brain volume and regional grey matter volume (GM). Our results showed that the ADHD patients had more regional GM in the bilateral thalamus relative to the controls. Post hoc analysis revealed that regional GM increase only linked to the iADHD subtype in the right thalamus and precentral gyrus. Besides, the right thalamus volume was positively related to inattentive severity in the iADHD. There were no group differences in global volume. Our results provide preliminary evidence that cerebral structural alterations are tied to uncomorbid ADHD subjects and predominantly attribute to iADHD subtype. Furthermore, the volume of the right thalamus may be relevant to inattentive symptoms in iADHD possibly related to a lack of inhibition of irrelevant sensory input.

CT Manifestations of Coronavirus Disease (COVID-19) Pneumonia and Influenza Virus Pneumonia: A Comparative Study.

OBJECTIVE. The purpose of this study was to investigate differences in CT manifestations of coronavirus disease (COVID-19) pneumonia and those of influenza virus pneumonia. MATERIALS AND METHODS. We conducted a retrospective study of 52 patients with COVID-19 pneumonia and 45 patients with influenza virus pneumonia. All patients had positive results for the respective viruses from nucleic acid testing and had complete clinical data and CT images. CT findings of pulmonary inflammation, CT score, and length of largest lesion were evaluated in all patients. Mean density, volume, and mass of lesions were further calculated using artificial intelligence software. CT findings and clinical data were evaluated. RESULTS. Between the group of patients with COVID-19 pneumonia and the group of patients with influenza virus pneumonia, the largest lesion close to the pleura (i.e., no pulmonary parenchyma between the lesion and the pleura), mucoid impaction, presence of pleural effusion, and axial distribution showed statistical difference (p < 0.05). The properties of the largest lesion, presence of ground-glass opacity, presence of consolidation, mosaic attenuation, bronchial wall thickening, centrilobular nodules, interlobular septal thickening, crazy paving pattern, air bronchogram, unilateral or bilateral distribution, and longitudinal distribution did not show significant differences (p > 0.05). In addition, no significant difference was seen in CT score, length of the largest lesion, mean density, volume, or mass of the lesions between the two groups (p > 0.05). CONCLUSION. Most lesions in patients with COVID-19 pneumonia were located in the peripheral zone and close to the pleura, whereas influenza virus pneumonia was more prone to show mucoid impaction and pleural effusion. However, differentiating between COVID-19 pneumonia and influenza virus pneumonia in clinical practice remains difficult.

Exploring white matter functional networks in children with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder has been identified to involve the impairment of large-scale functional networks within grey matter, and recent studies have suggested that white matter, which also encodes neural activity, can manifest intrinsic functional organization similar to that of grey matter. However, the alterations in white matter functional networks in attention-deficit/hyperactivity disorder remain unknown. We recruited a total of 99 children, including 66 drug-naive patients and 33 typically developing controls aged from 6 to 14, to characterize the alterations in functional networks within white matter in drug-naive children with attention-deficit/hyperactivity disorder. Using clustering analysis, resting-state functional MRI data in the white matter were parsed into different networks. Intrinsic activity within each network and connectivity between networks and the associations between network activity strength and clinical symptoms were assessed. We identified eight distinct white matter functional networks: the default mode network, the somatomotor network, the dorsal attention network, the ventral attention network, the visual network, the deep frontoparietal network, the deep frontal network and the inferior corticospinal-posterior cerebellum network. The default mode, somatomotor, dorsal attention and ventral attention networks showed lower spontaneous neural activity in patients. In particular, the default mode network and the somatomotor network largely showed higher connectivity with other networks, which correlated with more severe hyperactive behaviour, while the dorsal and ventral attention networks mainly had lower connectivity with other networks, which correlated with poor attention performance. In conclusion, there are two distinct patterns of white matter functional networks in children with attention-deficit/hyperactivity disorder, with one being the hyperactivity-related hot networks including default mode network and somatomotor network and the other being inattention-related cold networks including dorsal attention and ventral attention network. These results extended upon our understanding of brain functional networks in attention-deficit/hyperactivity disorder from the perspective of white matter dysfunction.

Effects of the 2-Repeat Allele of the DRD4 Gene on Neural Networks Associated With the Prefrontal Cortex in Children With ADHD.

Objective: Genetic variation, especially polymorphism of the dopamine D4 receptor gene (DRD4), has been linked to deficits in self-regulation and executive functions and to attention deficit hyperactivity disorder (ADHD), and is related to the structural and functional integrity of the default mode network (DMN), the executive control network (ECN) and the sensorimotor network (SMN). The aim of this study was to explore the effects of the 2-repeat allele of the DRD4 gene on brain network connectivity and behaviors in children with ADHD. Methods: Using independent component analysis (ICA) and dimension analyses, we examined resting-state functional magnetic resonance imaging (fMRI) data obtained from 52 Asian medicine-naive children with ADHD (33 2-repeat absent and 19 2-repeat present). Results: We found that individuals with 2-repeat absent demonstrated increased within-network connectivity in the right precuneus of the DMN, the right middle frontal gyrus (MFG) of the SMN compared with individuals with 2-repeat present. Within the ECN, 2-repeat absent showed decreased within-network connectivity in the left inferior frontal gyrus (IFG) and the left anterior cingulate cortex. A deeper study found that connectivity strength of the left IFG was directly proportional to the Stroop reaction time in 2-repeat absent group, and as well as the right MFG in 2-repeat present group. Conclusion: Polymorphisms of the DRD4 gene, specifically 2-repeat allele, had effects on the ECN, the SMN and the DMN, especially in the prefrontal cortex (PFC) circles. ADHD children with DRD4 2-repeat allele have aberrant resting-state within-network connectivity patterns in the left IFG and the right MFG related to dysfunction in inattention symptom. This study provided novel insights into the neural mechanisms underlying the effects of DRD4 2-repeat allele on ADHD.

Dopamine D4 Receptor Gene Associated with the Frontal-Striatal-Cerebellar Loop in Children with ADHD: A Resting-State fMRI Study.

Attention deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that has been linked to the dopaminergic system. This study aimed to investigate the effects of regulation of the dopamine D4 receptor (DRD4) on functional brain activity during the resting state in ADHD children using the methods of regional homogeneity (ReHo) and functional connectivity (FC). Resting-state functional magnetic resonance imaging data were analyzed in 49 children with ADHD. All participants were classified as either carriers of the DRD4 4-repeat/4-repeat (4R/4R) allele (n = 30) or the DRD4 2-repeat (2R) allele (n = 19). The results showed that participants with the DRD4 2R allele had decreased ReHo bilaterally in the posterior lobes of the cerebellum, while ReHo was increased in the left angular gyrus. Compared with participants carrying the DRD4 4R/4R allele, those with the DRD4 2R allele showed decreased FC to the left angular gyrus in the left striatum, right inferior frontal gyrus, and bilateral lobes of the cerebellum. The increased FC regions included the left superior frontal gyrus, medial frontal gyrus, and rectus gyrus. These data suggest that the DRD4 polymorphisms are associated with localized brain activity and specific functional connections, including abnormality in the frontal-striatal-cerebellar loop. Our study not only enhances the understanding of the correlation between the cerebellar lobes and ADHD, but also provides an imaging basis for explaining the neural mechanisms underlying ADHD in children.

Disrupted Control-Related Functional Brain Networks in Drug-Naive Children with Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disease featuring executive control deficits as a prominent neuropsychological trait. Executive functions are implicated in multiple sub-networks of the brain; however, few studies examine these sub-networks as a whole in ADHD. By combining resting-state functional MRI and graph-based approaches, we systematically investigated functional connectivity patterns among four control-related networks, including the frontoparietal network (FPN), cingulo-opercular network, cerebellar network, and default mode network (DMN), in 46 drug-naive children with ADHD and 31 age-, gender-, and intelligence quotient-matched healthy controls (HCs). Compared to the HCs, the ADHD children showed significantly decreased functional connectivity that primarily involved the DMN and FPN regions and cross-network long-range connections. Further graph-based network analysis revealed that the ADHD children had fewer connections, lower network efficiency, and more functional modules compared with the HCs. The ADHD-related alterations in functional connectivity but not topological organization were correlated with clinical symptoms of the ADHD children and differentiated the patients from the HCs with a good performance. Taken together, our findings suggest a less-integrated functional brain network in children with ADHD due to selective disruption of key long-range connections, with important implications for understanding the neural substrates of ADHD, particularly executive dysfunction.